Biochemical princeples of infertility

1
Biochemical princeples of infertility
2
Objectives

• Define primary and secondary infertility
• Describe the causes of infertility
• Diagnosis and management of infertility

3
Requirements for Conception

• Production of healthy egg and sperm
• Unblocked tubes that allow sperm to reach the egg
• The sperms ability to penetrate and fertilize the
  egg
• Implantation of the embryo into the uterus
• Finally a healthy pregnancy

4
Infertility

• The inability to conceive following unprotected
  sexual intercourse
• 1 year (age lt 35) or 6 months (age gt35)
• Affects 15 of reproductive couples
• 6.1 million couples
• Men and women equally affected

5
Infertility - Statistics

• causes are identified in 90 of patients
• pregnancy results in 40 of those
• 30 of couples have male AND female factors
• Of 100 subfertile couples the break down is as
  follows
• 40 male factor etiology
• 20 female hormonal imbalance
• 30 female peritoneal factor
• 5 hostile cervical environment
• 5 unexplained
• psychological impact can be significant

6
Infertility

• Reproductive age for women
• Generally 15-44 years of age
• Fertility is approximately halved between 37th
  and 45th year due to alterations in ovulation
• 20 of women have their first child after age 30
• 1/3 of couples over 35 have fertility problems
• Ovulation decreases
• Health of the egg declines
• With the proper treatment 85 of infertile
  couples can expect to have a child

7
Infertility

• Primary infertility
• a couple that has never conceived
• Secondary infertility
• infertility that occurs after previous pregnancy
  regardless of outcome

8
Causes for infertility

• Male
• Drugs
• Tobacco
• Health problems
• Radiation/Chemotherapy
• Age
• Enviromental factors
• Pesticides
• Lead

• Female
• Age
• Stress
• Poor diet
• Athletic training
• Over/underweight
• Tobacco
• STDs
• Health problems

9
Causes of Infertility

• Anovulation (10-20)
• Anatomic defects of the female genital tract
  (30)
• Abnormal spermatogenesis (40)
• Unexplained (10-20)

10
Evaluation of the Infertile couple

• History and Physical exam
• Semen analysis
• Thyroid and prolactin evaluation
• Determination of ovulation
• Basal body temperature record
• Serum progesterone
• Ovarian reserve testing
• Hysterosalpingogram

11
Abnormalities of Spermatogenesis
12
Normal

• Sperm made in seminiferous
• tubules
• Travel to
• epididymis to
• mature

13
Normal

• Sperm exit through vas deferens
• Semen produced in prostate gland, seminal glands,
  cowpers glands
• Sperm only 5 of ejaculation
• Sperm can live 5-7 days

14
Male Factor

• 40 of the cause for infertility
• Sperm is constantly produced by the germinal
  epithelium of the testicle
• Sperm generation time 73 days
• Sperm production is thermoregulated
• 1 F less than body temperature
• Both men and women can produce anti-sperm
  antibodies which interfere with the penetration
  of the cervical mucus

15
Semen Analysis (SA)

• Obtained by masturbation
• Provides immediate information
• Quantity
• Quality
• Density of the sperm
• Morphology
• Motility
• Abstain from coitus 2 to 3 days
• Collect all the ejaculate
• Analyze within 1 hour
• A normal semen analysis excludes male factor 90
  of the time

16
Normal Values for SA

• Volume
• Sperm Concentration
• Motility
• Viscosity
• Morphology
• pH
• WBC

• 2.0 ml or more
• 20 million/ml or more
• 50 forward progression
• 25 rapid progression
• Liquification in 30-60 min
• 30 or more normal forms
• 7.2-7.8
• Fewer than 1 million/ml

17
Causes for Abnormal SA

• No sperm
• Klinefelters syndrome
• Sertoli only syndrome
• Ductal obstruction
• Hypogonadotropic-hypogonadism

• Few sperm
• Genetic disorder
• Endocrinopathies
• Varicocele
• Exogenous (e.g., Heat)

Abnormal Count
18
Continues causes for abnormal SA

• Abnormal Morphology
• Varicocele
• Stress
• Infection (mumps)
• Abnormal Motility
• Immunologic factors
• Infection
• Defect in sperm structure
• Poor liquefaction
• Varicocele

• Abnormal Volume
• No ejaculate
• Ductal obstruction
• Retrograde ejaculation
• Ejaculatory failure
• Hypogonadism
• Low Volume
• Obstruction of ducts
• Absence of vas deferens
• Absence of seminal vesicle
• Partial retrograde ejaculation
• Infection

19
Causes for male infertility

• 42 varicocele
• repair if there is a low count or decreased
  motility
• 22 idiopathic
• 14 obstruction
• 20 other (genetic
• abnormalities)

20
Abnormal Semen Analysis

• Oligospermia
• Anatomic defects
• Endocrinopathies
• Genetic factors
• Exogenous (e.g. heat)
• Abnormal volume
• Retrograde ejaculation
• Infection
• Ejaculatory failure

• Azoospermia
• Klinefelters (1 in 500)
• Hypogonadotropic-hypogonadism
• Ductal obstruction (absence of the Vas deferens)

21
Evaluation of Abnormal SA

• Repeat semen analysis in 30 days
• Physical examination
• Testicular size
• Varicocele
• Laboratory tests
• Testosterone level
• FSH (spermatogenesis- Sertoli cells)
• LH (testosterone- Leydig cells)
• Referral to urology

22
Evaluation of Ovulation
23
Female Reproductive System

• Ovaries
• Two organs that produce eggs
• Size of almond
• 30,000-40,000 eggs
• Eggs can live for 12-24 hours

24
Menstruation

• Ovulation occurs 13-14 times per year
• Menstrual cycles on average are Q 28 days with
  ovulation around day 14
• Luteal phase
• dominated by the secretion of progesterone
• released by the corpus luteum
• Progesterone causes
• Thickening of the endocervical mucus
• Increases the basal body temperature (0.6 F)
• Involution of the corpus luteum causes a fall in
  progesterone and the onset of menses

25
(No Transcript)
26
Ovulation

• A history of regular menstruation suggests
  regular ovulation
• The majority of ovulatory women experience
• fullness of the breasts
• decreased vaginal secretions
• abdominal bloating
• Absence of PMS symptoms may suggest anovulation

• mild peripheral edema
• slight weight gain
• depression

27
(No Transcript)
28
Diagnostic studies to confirm Ovulation

• Basal body temperature
• Inexpensive
• Accurate
• Endometrial biopsy
• Expensive
• Static information

• Serum progesterone
• After ovulation rises
• Can be measured
• Urinary ovulation-detection kits
• Measures changes in urinary LH
• Predicts ovulation but does not confirm it

29
Basal Body Temperature

• Excellent screening tool for ovulation
• Biphasic shift occurs in 90 of ovulating women
• Temperature
• drops at the time of menses
• rises two days after the lutenizing hormone (LH)
  surge
• Ovum released one day prior to the first rise
• Temperature elevation of more than 16 days
  suggests pregnancy

30
(No Transcript)
31
Serum Progesterone

• Progesterone starts rising with the LH surge
• drawn between day 21-24
• Mid-luteal phase
• gt10 ng/ml suggests ovulation

32
Salivary Estrogen TCI Ovulation Tester- 92
accurate
33
Add Saliva Sample
34
(No Transcript)
35
(No Transcript)
36
Non-Ovulatory Saliva Pattern
37
High Estrogen/ Ovulatory Saliva Pattern
38
Anovulation
39
Anovulation Symptoms Evaluation

• Irregular menstrual cycles
• Amenorrhea
• Hirsuitism
• Acne
• Galactorrhea
• Increased vaginal secretions

• Follicle stimulating hormone
• Lutenizing hormone
• Thyroid stimulating hormone
• Prolactin
• Androstenedione
• Total testosterone

• Order the appropriate tests based on the clinical
  indications

40
Anatomic Disorders of the Female Genital Tract
41
Sperm transport, Fertilization, Implantation

• The female genital tract is not just a conduit
• facilitates sperm transport
• cervical mucus traps the coagulated ejaculate
• the fallopian tube picks up the egg
• Fertilization must occur in the proximal portion
  of the tube
• the fertilized oocyte cleaves and forms a zygote
• enters the endometrial cavity at 3 to 5 days
• Implants into the secretory endometrium for
  growth and development

42
Fertilization
43
Implantation
44
(No Transcript)
45
Acquired Disorders

• Acute salpingitis
• Alters the functional integrity of the fallopian
  tube
• N. gonorrhea and C. trachomatis
• Intrauterine scarring
• Can be caused by curettage
• Endometriosis, scarring from surgery, tumors of
  the uterus and ovary
• Fibroids, endometriomas
• Trauma

46
Congenital Anatomic Abnormalities
47
Hysterosalpingogram

• An X-ray that evaluates the internal female
  genital tract
• architecture and integrity of the system
• Performed between the 7th and 11th day of the
  cycle
• Diagnostic accuracy of 70

48
Hysterosalpingogram

• The endometrial cavity
• Smooth
• Symmetrical
• Fallopian tubes
• Proximal 2/3 slender
• Ampulla is dilated
• Dye should spill promptly

49
HSG Tubal Infertility
50
Unexplained infertility

• 10 of infertile couples will have a completely
  normal workup
• Pregnancy rates in unexplained infertility
• no treatment 1.3-4.1
• clomid and intrauterine insemination 8.3
• gonadotropins and intrauterine insemination 17.1